Alpha fetoprotein is produced by the fetal liver and circulates maternal serum at high levels. Immunosuppressive and antiestrogenic activity of this protein may influence subsequent risk of breast cancer. The proposed study is designed to test the hypothesis that a high maternal serum level of alpha fetoprotein during pregnancy is protective against subsequent estrogen-receptor-positive breast cancer. Stored sera from women who were pregnant approximately thirty years ago will be used to assay for alpha fetoprotein. We propose a case-control study nested with the child Health and Development Study cohort, assembled by the University of California, Berkeley. Cases will be women with histologically confirmed breast cancer identified through the California Tumor Registry. Controls will be other members of the cohort free of breast cancer selected on the basis of California residency, and frequency matched to cases on gestational age at blood draw, age of woman at time of pregnancy, and race. Information on major risk factors for breast cancer, available from computerized questionnaire data on cohort members, will be used in stratified analyses and unconditional logistic regression. Results of this study may provide new strategies for preventing a disease that is currently the second leading cause of death for women in the United States.